Pregnancy-related complications and perinatal outcomes resulting from transfer of cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis.

OBJECTIVE: To provide an updated comparison of pregnancy-related complications and adverse perinatal outcomes of pregnancies conceived after frozen embryo transfer (FET) versus fresh embryo transfer (fresh ET). DESIGN: Meta-analysis. SETTING: University. PATIENT(S): Pregnancies resulting from FET versus fresh ET. INTERVENTIONS(S): Pubmed, Embase, Cochrane Library, Google Scholar, and Chinese databases, including the China National Knowledge Infrastructure Database, Wanfang, and Chinese Scientific Journals Full-Text Database were searched by two independent reviewers from January 1980 to September 2017. The results were expressed as risk ratios with 95% confidence intervals. MAIN OUTCOME MEASURE(S): Pregnancy-related complications and perinatal outcomes. RESULT(S): Our search retrieved 1,397 articles, of which 31 studies were included. Pregnancies resulting from FET were associated with lower relative risks of placenta previa, placental abruption, low birth weight, very low birth weight, very preterm birth, small for gestational age, and perinatal mortality compared with fresh ET. Pregnancies occurring from FET were associated with increased risks of pregnancy-induced hypertension, postpartum hemorrhage, and large for gestational age compared with fresh ET. The risks of gestational diabetes mellitus, preterm premature rupture of the membranes, and preterm birth (PTB) showed no differences between the two groups. CONCLUSION(S): Our analysis demonstrated that FET results in lower risks of placenta previa, placental abruption, low birth weight, very low birth weight, very preterm birth, small for gestational age, and perinatal mortality than fresh ET, some differences that are attributed to the increased risks of pregnancy-induced hypertension, large for gestational age, and postpartum hemorrhage. Although cryotechnology keeps improving, for comprehensive consideration, individual approaches remain appropriate to balance the options of FET or fresh ET at present.

In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study.

OBJECTIVE: To determine the clinical value of preimplantation genetic diagnosis for aneuploidy screening (PGD-A) in women of advanced maternal age (AMA; between 38 and 41 years). DESIGN: This was a multicenter, randomized trial with two arms: a PGD-A group with blastocyst transfer, and a control group with blastocyst transfer without PGD-A. SETTING: Private reproductive centers. PATIENT(S): A total of 326 recruited patients fit the inclusion criteria, and 205 completed the study (100 in the PGD-A group and 105 in the control group). INTERVENTION(S): Day-3 embryo biopsy, array comparative genomic hybridization, blastocyst transfer, and vitrification. MAIN OUTCOME MEASURE(S): Primary outcomes were delivery and live birth rates in the first transfer and cumulative outcome rates. RESULT(S): The PGD-A group exhibited significantly fewer ETs (68.0% vs. 90.5% for control) and lower miscarriage rates (2.7% vs. 39.0% for control). Delivery rate after the first transfer attempt was significantly higher in the PGD-A group per transfer (52.9% vs 24.2%) and per patient (36.0% vs. 21.9%). No significant differences were observed in the cumulative delivery rates per patient 6 months after closing the study. However, the mean number of ETs needed per live birth was lower in the PGD-A group compared with the control group (1.8 vs. 3.7), as was the time to pregnancy (7.7 vs. 14.9 weeks). CONCLUSION(S): Preimplantation genetic diagnosis for aneuploidy screening is superior compared with controls not only in clinical outcome at the first ET but also in dramatically decreasing miscarriage rates and shortening the time to pregnancy.

Oocyte donation recipients of very advanced age: perinatal complications for singletons and twins.

OBJECTIVE: To compare maternal, obstetric, and neonatal outcomes between women who underwent oocyte donation at or after age 50 years and from 45 through 49 years. DESIGN: Single-center, retrospective cohort study. SETTING: Maternity hospital. PATIENT(S): Forty women aged 50 years and older ("older group") and 146 aged 45-49 years ("younger group"). INTERVENTION(S): Comparison between the older and younger groups, globally and after stratification by type of pregnancy (singleton/twin pregnancy). MAIN OUTCOME MEASURE(S): Maternal, obstetric, and neonatal outcomes. RESULT(S): The rate of multiple-gestation pregnancies was similar in both groups (35% in the older and 37.7% in the younger group). We observed no significant difference globally between the two groups for outcomes, except for the mean duration of postpartum hospitalization, which was significantly longer among the older women (mean ± SD, 9.5 ± 7.4 days vs. 6.8 ± 4.4 days). The rates of isolated pregnancy-related hypertension and of fetal growth restriction in singleton pregnancies were statistically higher in the older than in the younger group (19.2% vs. 5.5%, and 30.7% vs. 14.3%, respectively). Complication rates with twin pregnancies were similar between groups and very high compared with singleton pregnancies. CONCLUSION(S): Complication rates were similar among women aged 50 years and older and those aged 45-49 years. Nonetheless, given the high rate of complication in both groups, especially among twin pregnancies, single embryo transfer needs to be encouraged for oocyte donations after age 45 years.

Morbidity and mortality of very low birth weight infants in Taiwan-Changes in 15 years: A population based study.

BACKGROUND/PURPOSE: Very low birth weight (VLBW) infants account for over 50% of perinatal deaths in Taiwan. This study aimed to identify changes in parental characteristics, perinatal conditions, mortality, and major neonatal morbidities for VLBW infants in Taiwan, and to highlight the challenges faced by patients, families, and caregivers. METHODS: We conducted a retrospective cohort study to investigate the mortality and morbidity of VLBW infants registered in the Taiwan Premature Infant Follow-up Network from 1997 through 2011. The exclusion criteria included congenital anomalies and chromosome anomalies. Continuous data was represented as mean ± SD, and changes over time in the variables were tested using one-way analysis of variance, with p < 0.05 considered statistically significant. RESULTS: A total of 13,159 VLBW infants were enrolled. We found significant increases over time in the parental age and educational level, in vitro fertilization, first livebirth, multiple births, maternal transfer, cesarean section, and complete antenatal steroid use. Apgar scores at 1 minute and 5 minutes after birth increased, and the intubation rate decreased gradually. Decreasing mortality over time for each successive period was demonstrated. Incidence of some morbidities increased, such as respiratory distress syndrome and patent ductus arteriosus; in contrast, incidence of others decreased, such as sepsis, necrotizing enterocolitis, intraventricular hemorrhage, and chronic lung disease. However, retinopathy of prematurity (ROP) incidence remained constant. CONCLUSION: Although the mortality and most of the morbidity of VLBW infants improved over time, the incidence of ROP remained constant. This requires us to further evaluate our strategy for preventing ROP in the future.

Fatal ovarian hyperstimulation syndrome in an anonymous egg donor.

Ovarian hyperstimulation syndrome is a rare, but potentially life-threatening iatrogenic disorder arising from ovulation induction or ovarian hyperstimulation for assisted reproduction techniques. We report a case of a 26-year-old multiparous woman, an anonymous egg donor, who died a few hours after undergoing a procedure to donate eggs at an in vitro fertilization clinic. Her husband alleged that medical negligence had led to her death. The autopsy confirmed death due to ovarian hyperstimulation syndrome. We know of no previous descriptions of fatal ovarian hyperstimulation syndrome in an anonymous egg donor in medico-legal literature.

Donor oocytes are associated with preterm birth when compared to fresh autologous in vitro fertilization cycles in singleton pregnancies.

OBJECTIVE: To use a national registry to examine the role of oocyte donation on pregnancy outcomes in singleton pregnancies. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Women undergoing autologous cycles and donor oocyte recipients in the United States from 2008-2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, birth weight <2,500 g, small for gestational age birthweight, perinatal death. RESULT(S): The rates of preterm delivery and low birthweight for all members of this cohort were higher than the US national average. Pregnancies resulting from oocyte donation were significantly more likely to end before 34 weeks' and 37 weeks' gestation (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.03-1.64 for 34 weeks' gestation, adjusted OR = 1.28, 95% CI = 1.12-1.46 for 37 weeks' gestation), and to result in infants weighing <2,500 g (adjusted OR = 1.21, 95% CI = 1.02-1.44). However, once gestational age at delivery is accounted for, these infants are actually at decreased risk of having a small for gestational age birthweight (adjusted OR = 0.72, 95% CI = 0.58-0.89) and of perinatal death (adjusted OR = 0.29, 95% CI = 0.09-0.94). CONCLUSION(S): Data from a national cohort indicate that donor oocyte recipients are more likely to deliver preterm when compared with autologous patients. The effect of donor oocyte donation on birthweight is likely a function of an increased rate of preterm delivery among this population.

Impact of single embryo transfer policy on perinatal outcomes in fresh and frozen cycles-analysis of the Japanese Assisted Reproduction Technology registry between 2007 and 2012.

OBJECTIVE: To investigate whether the introduction of single embryo transfer (SET) policy in Japan has improved perinatal outcomes. DESIGN: A retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 140,718 live births and 510 stillbirths (after 22 weeks of gestation) conceived by assisted reproductive technology in Japan between 2007 and 2012 were reviewed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm birth (PTB), low birth weight (LBW), very low birth weight (VLBW), small for gestational age (SGA), large for gestational age (LGA), perinatal mortality, and other pregnancy complications. RESULT(S): The rate of SET increased significantly from 52.2% in 2007 to 82.6% in 2012, while the rate of multiple pregnancy decreased significantly from 10.7% to 4.1% over the same period. The rates of PTB, LBW, and SGA decreased significantly, while that of LGA increased. Perinatal mortality decreased from 0.70% to 0.40% in fresh cycles, while that of frozen cycles did not change. Double ET or more was associated with a significantly increased risk for multiple pregnancy, placenta accreta, preterm premature rupture of membrane, cesarean section (CS), PTB, LBW, SGA, and early neonatal death compared with SET. Compared with before the SET policy was launched, the risks of multiple pregnancy, CS, early PTB before 32 weeks, LBW, VLBW, and SGA were significantly decreased after the policy was launched, with significant interactions of fresh/frozen status. CONCLUSION(S): The results suggest that the SET policy improved perinatal outcomes in Japan. The impact of SET policy was different in fresh and frozen cycles for several perinatal outcomes.

Gestational carrier BMI and reproductive, fetal and neonatal outcomes: are the risks the same with increasing obesity?

OBJECTIVE: Data suggest that female obesity impairs uterine receptivity and increases the risk of fetal and neonatal mortality. We analyzed the reproductive outcomes of gestational carriers (GCs) undergoing donated oocytes and assisted reproductive technology according to body mass index (BMI). DESIGN: A retrospective analysis of 163 GCs undergoing 226 in vitro fertilization (IVF) and embryo transfer cycles. METHODS: GCs undergoing in vitro fertilization and embryo transfer cycles were analyzed and divided according to their BMI (healthy weight: 20-24.9 kg m(-2) (n=77 in 114 cycles); overweight: 25-29.9 kg m(-)(2) (n=55 in 71 cycles); and obese: 30-35 kg m(-)(2) (n=31 in 41 cycles)). All GCs underwent a complete medical evaluation and were cleared for pregnancy before being selected. Overweight and obese GCs also underwent a metabolic screening, including an oral glucose tolerance test and lipid profile. The main outcomes measured were clinical pregnancy and live birth rates, antenatal and neonatal outcomes. RESULTS: Clinical pregnancy and live birth rates were similar despite increasing BMI. There were no statistically significant differences in the implantation rates, clinical pregnancy rates or live birth rates per embryo transfer among patients in the three BMI groups. In the healthy weight, overweight and obese GCs, the clinical pregnancy rates per GC were 72%, 84% and 79%, and per embryo transfer rates were 52%, 49% and 56%, respectively; P=NS. The live birth rates per GC were 70%, 84% and 75%, and per embryo transfer rates were 50%, 49% and 53%, respectively; P=NS. Twin rates were similar between the groups (35%, 31% and 29%, respectively; P=NS). There were no differences in gestational diabetes, preterm admissions or cesarean section rates. Neonatal intensive care unit admissions were similar (11%, 13% and 12%, respectively; P=NS), and no maternal, neonatal or infant mortality occurred. CONCLUSIONS: These data show that increasing obesity does not impair the reproductive outcome in GC cycles. Larger sample size is indicated to verify these findings. Furthermore, this study suggests that the standard metabolic screening used for GCs may lead to selection of healthier patients compared with women of comparable BMI who conceive outside of a fertility clinic setting, indicating the metabolic profile, rather than BMI, may better explain differences in pregnancy outcomes.

The success rate of IVF has significantly improved over the last decade.

AIM: To demonstrate that success rates with in vitro fertilisation (IVF) have been improving despite decreasing the number of embryos transferred. MATERIALS AND METHODS: This was a retrospective cohort study comparing live birth outcomes for women who started IVF between 2001 and 2005 with women who started between 2006 and 2010, using life table analysis to allow for the fact that women had differing number of cycles of treatment. The data were obtained from a single IVF centre, Monash IVF Geelong, Victoria. The 2001-2005 cohort consisted of 233 women, and the 2006-2010 cohort consisted of 453 women who started IVF between the specified dates. The main outcome measure was a live birth. Life table analysis was used to estimate the cumulative probability of a live birth after each cycle. RESULTS: The estimate of cumulative live birth probability demonstrated that the chance of a live birth by cycle five was 75.8% in the 2001-2005 cohort, which significantly increased to 80.1% by cycle five in the 2006-2010 cohort (P = <0.05). There was a mean of 1.8 embryos transferred per embryo transfer in the 2001-2005 cohort, which decreased to a mean of 1.3 embryos transferred per embryo transfer in the 2006-2010 cohort. This was associated with a significant decrease in the multiple birth rate from 24.7% in the 2001-2005 cohort to 7.5% in the 2006-2010 cohort. CONCLUSION: The IVF success rate has significantly improved despite the number of embryos transferred being reduced. This study provides further support for elective single embryo transfers.

Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavage-stage embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of obstetric and perinatal complications in singleton pregnancies after the transfer of blastocyst-stage and cleavage-stage embryos generated through IVF. DESIGN: Systematic review. SETTING: University hospital. PATIENT(S): Singleton pregnancies resulting from ET at the blastocyst stage versus those at the cleavage stage. INTERVENTION(S): Medline, EMBASE, Cochrane Central Register of Clinical Trials DARE, and CINAHL (1980-2013) were searched. Two independent reviewers extracted data and assessed the methodological quality of the relevant studies using CASP scoring. Risk ratios and risk differences were calculated in Rev Man 5.1. MAIN OUTCOME MEASURE(S): Very preterm birth, preterm birth, small for gestational age, low birth weight, very low birth weight, congenital anomalies, perinatal mortality, preeclampsia, and placenta previa. RESULT(S): In vitro fertilization pregnancies occurring as a result of ET at the blastocyst stage were associated with a higher relative risk (RR; 95% confidence interval [CI]) of preterm (RR 1.27; 95% CI 1.22-1.31) and very preterm delivery (RR 1.22; 95% CI 1.10-1.35) in comparison with those resulting from the transfer of cleavage-stage embryos. The risk of growth restriction was lower in babies conceived through blastocyst transfer (RR 0.82; 95% CI 0.77-0.88). CONCLUSION(S): Data from observational studies show that ET at the blastocyst stage is associated with a higher risk of very preterm delivery. However, we were not able to adjust for confounders. Perinatal outcome data from existing randomized trials are needed to determine the safety of ET at the blastocyst stage compared with the cleavage stage.

Correlação entre os métodos de concepção, ocorrência e formas de tratamento das onfalopatias em bovinos: estudo retrospectivo / Correlation between conception methods, occurrence, and type o treatment of the umbilical diseases in cattle: a retrospective study

Alguns problemas têm sido observados nos bezerros produtos da técnica fertilização in vitro, dentre esses a elevada casuística de onfalopatias. A partir dessa observação, objetivou-se com este trabalho realizar um estudo retrospectivo da correlação entre os métodos de concepção e a ocorrência de onfalopatias em bovinos e descrever os resultados obtidos a partir dos tratamentos conservativo e cirúrgico. Foram utilizados 44 bovinos atendidos no Hospital Veterinário da Unesp, Campus de Araçatuba, com idade variando de um dia a 12 meses entre os anos de 2003 e 2007. Desses bovinos 27 eram provenientes de fertilização in vitro (FIV), 12 de inseminação artificial (IA), dois de monta natural (MN) e três de transferência de embriões (TE). O diagnóstico clínico-cirúrgico revelou que todos apresentavam afecções umbilicais, sendo 22 casos de persistência de úraco, oito de onfaloflebite, oito de hérnias umbilicais, cinco de onfalites e um de fibrose umbilical. Inicialmente e no pós-operatório administrou-se em todos os animais, uma vez ao dia, durante dez dias, 3mg/kg de ceftiofur sódico pela via intravenosa (IV). Nos casos de infecção grave ou irresponsiva a terapia antimicrobiana inicial, acrescentou-se 6,6mg/kg, durante sete dias de sulfato de gentamicina IV. A antissepsia do umbigo, com tintura de iodo a 2 por cento, foi instituída duas vezes ao dia, nos casos tratados conservativamente, enquanto que os bovinos submetidos à cirurgia receberam 1,1mg/kg de flunixin meglumine IV, uma vez ao dia, por cinco dias consecutivos. Dos 22 animais diagnosticados com persistência de úraco, 10 apresentavam drenagem de urina pelo umbigo e receberam 2mL de tintura de iodo 10 por cento no interior do úraco, sendo 15 tratados com a excisão cirúrgica, especialmente, devido à formação de divertículo vésico-uracal. Todos os animais que apresentavam onfaloflebite e hérnia umbilical foram submetidos à cirurgia...

Some problems have been observed in bovine products of the in vitro fertilization technical, among these, the high umbilical diseases casuistry. From this observation, the aim of this work was to accomplish a retrospective study of the correlation between the conception methods and the occurrence of umbilical diseases in bovines and describe the results obtained from the conservative and surgical treatments. For this 44 animals attended at Veterinary Teaching Hospital of Unesp Araçatuba, with age varying from one day to 12 months among the years of 2003 and 2007 were used, twenty seven were from in vitro fertilization (IVF), twelve were from artificial insemination (AI), two were from natural mounts and three were from embryo transfer. The clinical-surgical diagnosis of the animals revealed that all of them presented umbilical disorders, being 22 cases of urachus patent, eight omphalophlebitis, eight umbilical hernia, five omphalitis and one umbilical fibrosis. Before and at the postoperative period was administered in all animals once a day for ten days 3mg/kg of ceftiofur sodium IV. In cases of serious infection or lack of response of the initial antimicrobial therapy a complementary treatment during seven days with 6.6 mg/kg of gentamicin sulfate IV was carried out. The antisepsis of the umbilicus with tincture of iodine to 2 percent was carried out twice daily in cases treated clinically, with out surgery, while the animals underwent surgery received 1.1mg/kg of flunixin meglumine IV once daily for five consecutive days.Among the 22 animals diagnosed with urachus patent, 10 had urine drainage from the umbilicus and received 2mL of 10 percent tincture of iodine in the urachus, and 15 was treated with surgical excision, due to formation of diverticulum from the blader to urachus. All animals that were affected with omphalophlebitis and umbilical hernia were submitted to surgery...

Maternal death related to IVF in the Netherlands 1984-2008.

BACKGROUND: We assessed all deaths in the Netherlands that might have been related to IVF or to an IVF pregnancy in order to investigate this most serious complication. METHODS: All deaths related to IVF, within 1 year after IVF, from 1984 to 2008 were collected by sending a letter to all gynaecologists, and by retrieving data from a large cohort study examining the late effects of ovarian stimulation (OMEGA) and from the Dutch Maternal Mortality Committee. RESULTS: Six deaths were directly related to IVF (6/100,000), 17 deaths were directly related to the IVF pregnancy (42.5/100,000) and eight deaths were neither related to the IVF nor to the IVF-related pregnancy. The overall mortality in patients undergoing IVF procedures was lower than in the general population, whereas the overall mortality related to IVF pregnancies was higher than the maternal mortality in the general population. CONCLUSION: The decreased mortality is probably the result of a 'healthy female effect' in women undergoing IVF. The high maternal mortality in IVF pregnancies is probably related to the high number of multiple pregnancies and to the fact that (donor egg) IVF is successfully used in women who are older. The fact that only a few deaths directly related to IVF are reported in the literature whereas we observed six in the Netherlands indicates worldwide under-reporting of IVF-related mortality. We underline the importance of reporting all lethal cases to the European Society of Human Reproduction and Embryology Committee 'Safety and Quality after IVF'.

Maternal morbidity and mortality in in-vitro fertilization.

Pregnancies following in-vitro fertilization (IVF) are known to be at increased risk of a number of pregnancy- and delivery-related complications when compared with non-IVF pregnancies. Most of these complications seem to be due to underlying fertility problems. Ovarian stimulation carries a marked risk for two serious conditions - ovarian torsion and ovarian hyperstimulation syndrome - both of which are relatively rare. Although some common pregnancy complications show an up to five times increased risk over non-IVF pregnancies, the absolute frequencies are still low for most of these conditions. However, an increased risk of placenta praevia might be to some extent due to the IVF procedure. No long-terms effects on cancer risk or mortality can be linked to the IVF procedure, although follow-up time is still relatively short.

Factors influencing adverse perinatal outcomes in pregnancies achieved through use of in vitro fertilization.

OBJECTIVE: To determine the associations of specific components of IVF treatment with abnormal perinatal outcomes. DESIGN: Case-control study. SETTING: University-based and community-based infertility centers. PATIENT(S): All viable pregnancies achieved through IVF procedures performed between January 1999 and March 2004. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Infertility etiology, gonadotropin exposure, embryo manipulation, and quality. RESULT(S): Of 455 viable pregnancies identified during the study period, 435 met inclusion criteria. While adjusting for maternal age, race, parity, body mass index, infertility center, and year of IVF procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons. Ovarian hyperstimulation syndrome significantly increased the risk more than 3-fold (odds ratio = 3.14; 95% confidence interval, 1.08-9.14), while endometrial thickness was found to have a significant protective effect (odds ratio = 0.89; 95% confidence interval, 0.80-0.99). We found no effect of etiology of infertility, dose or type of medication used for stimulation, use of embryo-manipulation techniques, or quality on perinatal outcome. CONCLUSION(S): These data confirm and quantify the risk of perinatal morbidity associated with multiple births. After adjusting for multiple births, ovarian hyperstimulation syndrome and suboptimal endometrial development are associated with adverse outcomes in pregnancies achieved through IVF. Our findings suggest that it may be the endometrium rather than the embryo that influences fetal growth and perinatal outcomes after IVF.

In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality.

OBJECTIVE: To investigate obstetric characteristics, maternal morbidity and mortality among Swedish women giving birth after in vitro fertilisation (IVF) treatment. DESIGN: Register study. SETTING: Nationwide study in Sweden. SAMPLE: All women known to have had IVF in Sweden 1982-2001. METHODS: Using Swedish health registers, women who had given birth after IVF were identified from all Swedish IVF clinics and compared with all women who gave birth. Analysis was performed with the Mantel-Haenszel technique. MAIN OUTCOME MEASURES: Diagnoses during pregnancy, at delivery and at re-admission within 60 days after delivery and risk of cancer. RESULTS: IVF women had an increased risk of bleeding in early pregnancy [odds ratio (OR) = 4.59, 95% confidence interval (95% CI) 4.08-5.15] and of ovarian torsion during pregnancy (OR = 10.6, 5.69-10.7). They were also more likely to encounter pre-eclampsia (OR = 1.63, 1.53-1.74), placental abruption (2.17, 1.74-2.72), placenta praevia (3.65, 3.15-4.23), bleeding in association with vaginal delivery (1.40, 1.38-1.50) and premature rupture of membranes (PROM) (2.54, 2.34-2.76). Interventions including caesarean sections (1.38, 1.32-1.43) and induction of labour (1.37, 1.29-1.46) in singleton pregnancies was more frequent. The type of IVF method had little effect on these results, but there was a tendency for women who had received intra-cytoplasmatic sperm injection (ICSI) to have slightly fewer complications than women having standard IVF. There was a significant decrease in cancer risk after IVF (0.79, 0.69-0.91) but a suggested increase in the risk of ovarian cancer both before (2.70, 1.49-4.91) and after (2.08, 1.15-3.76) IVF. No change in mortality was observed. CONCLUSIONS: Women treated with IVF had an increased obstetric morbidity. This seems to contribute little to the well-known increased risk of preterm delivery.

Monozygotic twinning associated with day 5 embryo transfer in pregnancies conceived after IVF.

BACKGROUND: This study examines the association between day of embryo transfer and monozygotic (MZ) twinning. METHODS: We used a population-based sample of 108,36 IVF/embryo transfer procedures in which the patients oocytes' were freshly fertilized (non-frozen; non-donor) and 39,98 resultant pregnancies from US clinics in 1999 and 2000. Cases were pregnancies for which the number of fetal hearts observed on ultrasound exceeded the number of embryos transferred. These pregnancies were considered to contain at least one set of MZ twins. A total of 226 MZ pregnancies were compared with two control groups: 23,880 singleton pregnancies (one fetal heart) and 15,092 other multiple-gestation pregnancies (> or = 2 fetal hearts but the number of fetal hearts on ultrasound was less than or equal to the number of embryos transferred). RESULTS: Cases of presumed MZ multiple-gestation pregnancies were more likely to have had a day 5 embryo transfer compared with day 3 embryo transfers than singleton pregnancies [adjusted odds ratio (AOR) = 3.92, 95% confidence interval (CI) = 2.97-5.17] or other multiple-gestation pregnancies (AOR = 3.91, 95% CI = 2.96-5.17) conceived with IVF/embryo transfer. CONCLUSIONS: Day 5 embryo transfer may be associated with increased MZ twinning.

Mortality in a cohort of IVF patients.

BACKGROUND: Risks associated with IVF and related assisted reproduction technologies include complications of ovarian stimulation, surgical procedures and pregnancy itself. Serious complications are uncommon but may be potentially life threatening. The aims of this study were to compare the mortality rates of women who received IVF treatment, as well as those who were referred but were not treated, with the mortality rate in the general female population, to determine the maternal mortality rate following IVF conception and to establish whether any deaths had occurred as a result of treatment complications. METHODS: Deaths were identified in a cohort of 29 700 Australian IVF patients by record-linkage with the National Death Index and a cancer registry. RESULTS: The all-cause mortality rates in IVF patients (treated and untreated) were significantly lower than in the general female population of the same age. In treated women, 72 deaths were observed and 125 deaths were expected giving an age-standardized mortality ratio of 0.58 (95% confidence interval 0.48-0.69). Two maternal deaths were identified in the 42 days of the puerperium. Complications of ovarian hyperstimulation syndrome could not be directly related to any of the deaths identified in this cohort. CONCLUSIONS: As well as providing some reassurance about the safety of IVF treatments, the findings point to the existence of a 'healthy patient effect' whereby the unhealthiest women in the population are deterred from pregnancy and infertility treatment.

Assisted reproduction technology, multiple births, and adverse perinatal outcome.

The increase in the rate of multiple pregnancies in Australia in recent years is primarily due to the use of assisted reproduction technology. Compared to singleton births, fetal, neonatal, and perinatal mortality rates are 3-6 times higher in twins and 5-15 times higher in multiple births of a higher order. Cerebral palsy rates among survivors are six times higher in twins and twenty times higher in triplets. The increased risks in multiple pregnancies are not entirely explained by their higher prematurity and low birthweight rates. In Australia, the practice of transferring more than three embryos in any one assisted reproduction technology cycle has declined in recent years and, as a result, the number of multiple pregnancies from assisted reproduction technology has also declined. Nevertheless, assisted reproduction technology pregnancies remain to have poorer than normal outcome with regards to spontaneous abortion, ectopic pregnancy, preterm birth, low birthweight, and perinatal mortality. Infants born after assisted reproduction technology have a higher neonatal morbidity rate, including a greater requirement for assisted ventilation, and a higher long-term neurodevelopmental disability rate. These adverse outcomes following assisted reproduction technology are partly due to the increased risk of multiple pregnancy and partly due to preterm and low birthweight. This fact and the lack of evidence that the transfer of more than two embryos improves pregnancy rates, make it advisable to limit the number of embryos transferred to no more than one or two per cycle.